isotretinoin and Thyroid-Neoplasms

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells.. A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging.. In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARβ and RXRγ levels and downregulation of NF-κB targets genes. We show that bexarotene inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation.. This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-κB pathway.

Topics: Antigens, Differentiation; Antineoplastic Agents; Bexarotene; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Combined Modality Therapy; E1A-Associated p300 Protein; Female; Gene Expression Regulation, Neoplastic; Humans; Isotretinoin; Male; Middle Aged; Neoplasm Invasiveness; NF-kappa B; Receptors, Retinoic Acid; Retinoid X Receptor gamma; Tetrahydronaphthalenes; Thyroid Neoplasms; Transcription, Genetic; Transcriptional Activation; Treatment Outcome; Tretinoin

During thyroid tumor progression, cellular de-differentiation may occur and it is commonly accompanied by metastatic spread and loss of iodine uptake. Retinoic acid (RA) administration might increase iodine uptake in about 40% of patients, suggesting that RA could be a promising therapeutic option for radioiodine non-responsive thyroid carcinoma, although a prospective study with a long-term follow-up has not been reported. This was a clinical prospective study assessing the value of 13-cis-RA in patients with advanced thyroid carcinoma and its impact on major outcomes such as tumor regression and cancer-related death with a long-term follow-up of patients submitted to radioiodine (¹³¹I) therapy after RA administration. Sixteen patients with inoperable disease and no significant radioiodine uptake on post-therapy scan were selected. Patients were treated orally with 13-cis-RA at a dose of 1.0 to 1.5 mg·kg⁻¹·day⁻¹ for 5 weeks and then submitted to radioiodine therapy (150 mCi) after thyroxine withdrawal. A whole body scan was obtained 5 to 7 days after the radioactive iodine therapy. RECIST criteria were used to evaluate the response. An objective partial response rate was observed in 18.8%, a stable disease rate in 25% and a progression disease rate in 56.2%. Five patients died (62.5%) in the group classified as progression of disease. Progression-free survival rate (PFS) ranged from 72 to 12 months, with a median PFS of 26.5 months. RA may be an option for advanced de-differentiated thyroid cancer, due to the low rate of side effects.

Topics: Adult; Aged; Antineoplastic Agents; Combined Modality Therapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Radiation Tolerance; Thyroid Neoplasms; Treatment Outcome

Radioiodine (I-131) therapy is of proven efficacy for treatment of differentiated thyroid carcinoma (DTC). However, loss of differentiation in recurrent or metastatic DTC which decrease I-131 uptake may decrease the efficacy of I-131 therapy. Therefore, strategies to improve I-131 uptake are mandatory. This study is an open label clinical study to evaluate the effectiveness of 13-cis retinoic acid (13-cis RA) for improving I-131 uptake in recurrent or metastatic of DTC with defective I-131 uptake. Eleven patients (Age 27-66 years, M : F=4 : 7) were given 13-cis RA (1.5 mg/kg daily for 5 weeks), followed by 200 mCi (7.4 GBq) I-131 treatment. The differences of serum thyroglobulin (Tg) level and I-131 uptake on the post-treatment whole body scan (RxWBS) were compared before and after 13-cis RA therapy. Six out of 11 patients showed significantly increased (above 50%) Tg levels just after RA therapy. However, Tg levels a year after I-131 therapy were increased, stable and decreased in 7, 2 and 1 patients, respectively. Iodine uptake on RxWBS showed marginal improvement in only 2 patients and their Tg levels after one year follow-up increased. Most frequent adverse events were dry skin and lips. 13-cis RA partially restores I-131 uptake in few patients with recurrent or metastatic DTC. The use of 13-cis RA in current protocol has only limited usefulness and is not routinely recommended as currently used protocol.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Papillary, Follicular; Cell Differentiation; Chemotherapy, Adjuvant; Combined Modality Therapy; Female; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Radiotherapy Dosage; Thyroid Neoplasms; Treatment Failure; Treatment Outcome

Radio-iodine is effective in treating metastatic differentiated thyroid cancers. In 20% of cases, however, these tumours fail to take up radio-iodine, and treatment options are then limited. Failure of iodine uptake might be reversible using redifferentiating agents. Retinoids redifferentiate a variety of cell types and increase iodine uptake in thyroid tumour cells in vitro. The aim of this study was to assess whether oral isotretinoin could increase radio-iodine uptake in patients with iodine-uptake-negative metastatic thyroid cancer.. Patients who had iodine-uptake-negative metastatic papillary or follicular thyroid cancers were selected from the thyroid database at The Royal Marsden Hospital and enrolled to an open-label, non-randomised phase II trial. Sites of metastatic disease were assessed using computed tomography or magnetic resonance imaging, and absence of iodine uptake was confirmed using a diagnostic radio-iodine scan before study entry. In eligible patients, isotretinoin was prescribed at 1.5 mg/kg/day orally for 8 weeks. Response was assessed within 2 weeks of completing treatment with repeat radio-iodine scan. All patients were reviewed every 2 weeks during treatment for assessment of toxicity.. Sixteen patients were treated with isotretinoin between January 2001 and July 2002: nine with metastatic papillary thyroid cancer, five with metastatic follicular cancer and two with Hurthle cell carcinoma. Median age was 57 years. All patients tolerated 8 weeks of oral isotretinoin. Mucocutaneous side-effects and minor changes in biochemical or lipid profiles were documented in most patients. In one patient, radio-iodine uptake increased after retinoid administration; however, this was not large enough to permit a significant dose of iodine to be given to sites of metastatic disease. In the other 15 patients, no radio-iodine uptake was documented.. Treatment with isotretinoin does not reliably increase radio-iodine uptake in patients with metastatic thyroid cancer. This treatment alone does not enable radio-iodine to be used for further treatment.

Topics: Adenocarcinoma, Follicular; Administration, Oral; Adult; Aged; Carcinoma, Papillary; Combined Modality Therapy; Female; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Neoplasm Metastasis; Thyroid Neoplasms

Differentiated thyroid cancer is a malignant tumour that has a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery, radioiodine therapy and TSH suppressive medication is of proven efficacy. However, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumour grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumours may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy. Retinoic acids have been shown to exert re-differentiating effects on thyrocytes in various experimental studies and case reports, and it was on this basis that this pilot study was initiated. Patients with advanced thyroid cancer and without the therapeutic options of operation or radioiodide therapy were treated with 13- cis-retinoic acid at a dosage of 1.5 mg/kg body weight daily over 5 weeks. Parameters for assessment of the therapeutic effect were serum thyroglobulin (TG) levels, radioiodine uptake, and tumour size prior to and after retinoid treatment. Fifty patients were evaluated for response, classified as reduction in tumour size and TG levels, stable disease or disease progression. Thirteen patients showed a clear increase in radioiodine uptake, and eight a mild increase. TG levels were unchanged or decreased in 20 patients. Tumour size was assessable in 37 patients; tumour regression was observed in six, and there was no change in 22. In total, a response was seen in 19 patients (38%). Response to retinoid therapy did not always correlate with increased radioiodine uptake, so other direct antiproliferative effects have to be assumed. The encouraging results of the study and the low rate of side-effects with good tolerability of retinoids warrant further studies with altered inclusion criteria and employment of other redifferentiating drugs or combinations of agents.

Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Adult; Aged; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Chemotherapy, Adjuvant; Disease Progression; Female; Follow-Up Studies; Germany; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Pilot Projects; Prospective Studies; Radionuclide Imaging; Thyroglobulin; Thyroid Neoplasms; Treatment Outcome

The absence of iodine uptake in metastases of differentiated thyroid carcinoma makes them unresponsive to treatment with radioiodine 131I. In many of such cases symptomatic treatment remains the only available therapy. The results of studies on partial redifferentiation of metastases of thyroid cancer achieved after cis-retinoid acid therapy have drawn attention to the possibility of restoration of iodine uptake in metastases after pretreatment with cis-retinoic acid (Roaccutane). 5 patients with iodine uptake-negative metastases of differentiated thyroid carcinoma were given Roaccutane in a dose 1.5 mg/kg/24 h daily for 6 weeks before the therapy with radioiodine. In none of the patients restoration of radioiodine uptake in metastases has occurred as shown in post-therapeutic total body scintigraphy.

Topics: Adenocarcinoma, Follicular; Adult; Aged; Bone Neoplasms; Carcinoma, Papillary; Female; Humans; Iodine Radioisotopes; Isotretinoin; Lung Neoplasms; Premedication; Thyroglobulin; Thyroid Neoplasms

Retinoids, a large group of compounds structurally related to vitamin A, are able to induce redifferentiation of thyroid cancer cells. The aim of the study is to present our early results of retinoids redifferentiation therapy of thyroid cancer patients. In 15 patients with advanced thyroid cancer, whose cancer foci did not concentrate radioiodine, 13-cis retinoic acid (Roaccutan) was given for 6 weeks before radioiodine treatment. Radioiodine therapy was performed under exogenous TSH stimulation (Thyrogen). Three patients were treated twice. The planned retinoid dose was delivered to 11 patients. In the other four patients the reduction of retinoids dose was necessary due to severe side effects. In post-therapeutic scintigraphy radioiodine uptake was visible in two out of seven patients (29%) with lung metastases, in 5 out of 9 (56%) with locoregional disease and in two with bone metastases. On the whole, in 50% of patients reinduction of radioiodine uptake was visible, however, in most patients only a very discrete one. Thyroglobulin concentration before and after retinoids therapy did not differ significantly.. In a subgroup of patients 13-cis retinoic acid can induce radioiodine uptake, however, prospective studies in larger groups of patients are necessary to prove its clinical application.

Topics: Adult; Aged; Bone Neoplasms; Female; Humans; Iodine Radioisotopes; Isotretinoin; Lung Neoplasms; Male; Middle Aged; Premedication; Thyroglobulin; Thyroid Neoplasms

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid neoplasia that have lost radioiodine (131I) uptake with heterogeneous results.. Retrospective analysis of the recovery rate of 131I uptake after RA treatment in patients from 11 Spanish hospitals.. Twenty-seven patients (14 men, 13 women) with papillary [21], follicular [4], and oncocytic [2] thyroid cancer initially treated with total thyroidectomy plus 131I, and with 131I negative metastatic disease, were given 13-cis RA (0.66-1.5 mg/kg for 5-12 weeks) followed by a therapeutic 131I dose (3700-7400 MBq); 3 months later thyroglobulin levels and computed tomography imaging were performed.. In 9 out 27 cases (33%) (8 papillary, 1 follicular) optimal positive 131I scan was observed after RA treatment; in the remaining 18, 10 had a suboptimal uptake (7 papillary, 2 follicular, 1 oncocytic) and in the rest there was no 131I uptake recovery (6 papillary, 1 follicular, 1 oncocytic). In 17 positive responses to RA (either optimal or suboptimal) in which image follow-up was available, decrease or stabilization of metastatic growth was observed in 7, while tumor mass increased at short term in the remaining 10. No major side effects were detected.. Quite a high rate of 131I uptake recovery after RA treatment may be obtained in advanced differentiated thyroid cancer, but the potential modification of the natural course of the disease is uncertain. A better biological characterization of these tumors allowing the identification of potential responders to RA may improve the outcome of RA coadjuvant therapy.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Carcinoma, Papillary, Follicular; Cell Differentiation; Combined Modality Therapy; Female; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Radionuclide Imaging; Recovery of Function; Retrospective Studies; Thyroid Neoplasms; Treatment Outcome

The ability of thyroid cancer to incorporate radioiodine and to produce thyroglobulin (Tg) is an important tool for the diagnosis of tumor relapse. However, some patients show high serum Tg and negative whole body scan (WBS) since some specific thyroid properties may be lost during tumor progression. In these cases, a more careful diagnostic approach is necessary. Here, we report the case of a patient with undetectable serum Tg under levothyroxine (L-T4)-suppressive therapy and with a negative WBS 3 years after apparent thyroid remnant ablation. After detection of Tg mRNA in peripheral blood, the patient was re-investigated, and no suspicious lesions were detected by diagnostic WBS, neck ultrasonography, or thorax computerized tomography, except an elevation of serum Tg during hypothyroidism. Since retinoic acid (RA) is being used for the induction of radioiodine uptake by tumors expressing their receptors, we aimed to reveal the site of thyroid cancer relapse in this patient by isotretinoin administration. We demonstrate that apart from being a therapeutic option in some patients with thyroid cancer, RA can also be able to localize thyroid tissue in patients with high serum Tg and negative WBS.

Topics: Carcinoma, Papillary; Female; Humans; Isotretinoin; Middle Aged; Neoplasm Recurrence, Local; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms; Whole Body Imaging

We present a case in which a patient with disseminated well-differentiated papillary thyroid cancer developed severe thyroid-associated ophthalmopathy. Eight years after initial surgery and ablative radioiodine therapy the patient was found to have multiple pulmonary metastases. The metastases showed poor uptake of radioiodine. An attempt was made to use 13-cis-retinoic acid in order to achieve a redifferentiation of the thyroid cancer cells before recombinant human thyrotropin (rhTSH) stimulated radioiodine therapy. The treatment did not improve the uptake of radioiodine. However, approximately 2 weeks after completion of the treatment the patient experienced discomfort in her eyes and then over the next months she developed a severe ophthalmopathy. The analyses of TSH receptor antibodies and S-thyroglobulin simultaneously showed a pronounced increase. An association between therapy given and severe ophthalmopathy cannot be excluded.

Topics: Aged; Female; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Isotretinoin; Recombinant Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroidectomy; Thyrotropin

De-differentiated thyroid carcinoma is characterized by loss of thyroid-specific functions and properties. The therapeutic options for this type of thyroid cancer are limited and generally not efficient. Recent studies with retinoic acid (RA) have shown that this drug can induce re-differentiation of the thyrocyte and tumor regression after 131I therapy. The aim of the present study was to assess the effects of RA therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. A total of 5 patients (1 follicular carcinoma, 3 papillary carcinomas and 1 poorly differentiated carcinoma) were treated with isotretinoin (1.0 to 1.5 mg/kg/day) for 5 weeks and then submitted to radioiodine therapy. Three parameters for assessment of RA effects were established: a) reduction of serum thyroglobulin levels; b) increment of the post-therapeutic dose radioiodine uptake; c) tumor size regression after therapy. All patients completed the treatment and the most frequent side effects were dry skin and lips and hypertriglyceridemia. One patient showed satisfactory response (2 or more of the 3 criteria were reached) and a new cycle of RA was given. In two, just a partial response (1 criterion) was seen and the other patients did not respond. Based on these results, isotretinoin might be an option for de-differentiated thyroid cancer, with low rate of severe side effects, especially when compared with cytotoxic drugs. Aggressive thyroid cancer frequently needs multimodal adjuvant therapy.

Topics: Adenocarcinoma, Follicular; Adult; Aged; Carcinoma; Carcinoma, Papillary; Female; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Prospective Studies; Radionuclide Imaging; Thyroglobulin; Thyroid Neoplasms; Treatment Outcome

To evaluate the effectiveness of isotretinoin for improving (131)I uptake in recurrent/metastasized thyroid cancer with no/insufficient (131)I uptake.. Retrospective analysis of 25 patients treated between June 1999 and May 2001.. 15 female and 10 male patients were given isotretinoin at 1 mg/kg for 3 months, followed by (131)I treatment. All patients received a (131)I scan 72 h after administration, thyroglobulin measurement, chest X-ray and ultrasound of the neck, and some patients underwent a (18)F-fluorodeoxyglucose (FDG) positron emission tomography (n=14) and computed tomography scan of the chest (n=11).. In two out of 14 patients with raised thyroglobulin but no (131)I uptake, a slightly improved (131)I uptake was seen. In a further 11 patients an improvement of (131)I uptake of known lesions was desired or further non-(131)I-accumulating lesions were known. A dosimetrically relevant improvement of uptake was seen in three of these patients. (18)F-FDG uptake and thyroglobulin did not correlate with the success/failure of the isotretinoin treatment. Side effects including a strong "sunburn", cheilitis, mucositis, conjunctivitis and raised transaminases occurred in two-thirds of patients. They were of an overall tolerable level and were reversible after isotretinoin had been stopped.. From our clinical experience over a period of 2 years we conclude that the therapeutic effect of isotretinoin in thyroid cancer is certainly less than previously reported. An indiscriminate use of isotretinoin in all patients with otherwise untreatable thyroid cancer cannot be recommended.

Topics: Adenocarcinoma, Follicular; Adult; Aged; Aged, 80 and over; Carcinoma, Papillary; Female; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Retrospective Studies; Thyroid Neoplasms; Tomography, Emission-Computed; Treatment Outcome

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Adult; Aged; Antineoplastic Agents; Carcinoma, Papillary; Chemotherapy, Adjuvant; Female; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Radiopharmaceuticals; Thyroglobulin; Thyroid Neoplasms; Tomography, Emission-Computed

The prognosis of patients with metastasised follicular thyroid carcinoma (FTC) is limited, necessitating the search for new treatment options. Beneficial effects of retinoids have been suggested in thyroid cancer and the present study was performed to investigate the effects of retinoic acid (RA) on important determinants of metastatic behaviour in FTC: the disengagement of tumour cells from the primary tumour and the degradation of extracellular matrix, focusing on the role of the plasmin activation system and the integrin and E-cadherin families of attachment molecules. Three FTC cell lines were studied: FTC-133, derived from the primary tumour; and FTC-236 and FTC-238, derived from metastases. FTC cell lines were cultured with 0.1, 1 and 10 microM 13-cis-RA or with the solvent DMSO for 1 and 5 days. Extracellular matrix degradation by these cell lines was studied by assessing the 48-h release of radioactivity from (35)S-methionine labelled extracellular matrix proteins synthesised by the MC3T3 cell line coated onto plastic. The involvement of constituents of the plasmin activation system was investigated by semi-quantitative RT-PCR and zymography. Attachment to extracellular matrix was studied by determining the number of adhering FTC cells to extracellular matrix coated onto plastic, 3 h after seeding. The involvement of attachment molecules was studied by RT-PCR with primers for integrin subclasses and E-cadherin and immunofluorescence for E-cadherin. Five days culturing with 10 microM RA reduced the degradation of extracellular matrix significantly in all cell lines: FTC-133 by 35%, FTC-236 by 74% and FTC-238 by 31%. Zymography revealed diminished activity of urokinase type plasminogen activator (uPA) in FTC-236 and FTC-238, but not in FTC-133 cultured with RA. mRNA expression of the uPA receptor was diminished in FTC-236. In the attachment assay, 10 microM RA for 5 days increased the number of adherent cells to extracellular matrix significantly by 91% in FTC-133, 64% in FTC-236 and 87% in FTC-238. No effects of RA on integrin or E-cadherin mRNA expression were observed. Immunofluorescence, however, revealed enhanced organisation of E-cadherin along the cell membrane by RA treatment. In conclusion, the present study demonstrates beneficial effects of RA on important determinants of metastatic behaviour in FTC cell lines, e.g. decreased degradation of extracellular matrix which may in part be explained by effects on the plasmin activation system and

Topics: Adenocarcinoma, Follicular; Adult; Cadherins; Cell Adhesion; Extracellular Matrix; Fluorescent Antibody Technique; Humans; Isotretinoin; Male; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Neoplasms; Tumor Cells, Cultured

We present a case of increased I-131 uptake in a patient with papillary thyroid carcinoma with local recurrence and distant metastases after a second treatment with retinoic acid as a sign of redifferentiation of the tumor cells. When fine-needle aspiration cytology before and after a second course of retinoic acid treatment were compared, signs of tumor cell redifferentiation were found. This was accompanied by biochemical reexpression of thyroid marker proteins.

Topics: Carcinoma, Papillary; Humans; Iodine Radioisotopes; Isotretinoin; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Radionuclide Imaging; Thyroid Neoplasms

Due to a dedifferentiation of tumor cells, some thyroid carcinomas lose their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment. Retinoic acid (RA) is known to induce redifferentiation in various kinds of tumors and has been used recently in thyroid cancer.. Twelve patients (9 women, 3 men) with 6 papillary, 4 follicular and 2 mixed-cell type tumors (including 4 Hurthle cell carcinomas) were treated orally with RA (dose: 1.18 +/- 0.37 mg/kg body weight) for at least 2 mo before RI therapy. None of the patients could be treated with any other modality (RI, surgery, external radiation) when RA administration was started. Initially, clinically important tumor sites did not take up significant amounts of RI. Changes of RI uptake and thyroglobulin (Tg) serum values were determined. Glucose metabolism was followed with fluorodeoxyglucose (FDG) PET imaging in 10 patients before and in 5 patients after RA treatment.. In 2 patients, a significant RI uptake was induced by RA, and in another 3 patients a faint RI uptake was achieved (responder group). In 7 patients, no change of RI uptake was observed (nonresponder group). Median Tg was increased from 105-840 microg/liter during RA therapy in the responder group, which was significantly higher than the nonresponder group (173-134 microg/liter). FDG PET was positive in all 10 patients before RA therapy. PET showed variable patterns of changes (increase/decrease/disappearance) in glucose consumption related to RA response.. RA can induce RI uptake in some patients with RI negative thyroid carcinoma tumor sites. Response to RA is associated with a significantly higher increase of Tg, suggesting that a restoration of Tg synthesis can be addressed as a redifferentiation parameter in these patients.

Topics: Adenocarcinoma, Follicular; Aged; Carcinoma, Papillary; Case-Control Studies; Combined Modality Therapy; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Isotretinoin; Male; Radiopharmaceuticals; Thyroglobulin; Thyroid Neoplasms; Tomography, Emission-Computed

Topics: Aged; Antineoplastic Agents; Chemotherapy, Adjuvant; Humans; Isotretinoin; Lung Neoplasms; Lymphatic Metastasis; Male; Thyroid Neoplasms

Retinoic acids (RA) regulate growth and differentiation of normal epithelial tissue. They have been employed in anticancer treatment and showed positive effects in hematopoetic and various epithelial tumors. Experimental data with follicular thyroid tumor cells showed strong evidence of induction of differentiated cell function and antiproliferative effects. Based on these data a consecutive series of 10 patients with advanced thyroid carcinoma were treated with 13-cis-retinoic acid (Roaccutan) 1.5 mg/kg body weight for six weeks. Follow-up demonstrated renewed uptake of radioiodine in 4 of 10 patients allowing performance of further radioiodine therapy. Reduction in tumor size due to antiproliferative effects of RA could not yet be verified.

Topics: Adenoma; Aged; Carcinoma, Papillary; Cell Differentiation; Female; Humans; Iodine Radioisotopes; Isotretinoin; Male; Middle Aged; Thyroid Neoplasms